(A) Illustration of two models of post-infectious hydrocephalus (PIH). Insertion of an infusion pump in the lateral ventricle (LV) for E. coli+LPS, E. coli−LPS, LPS, or artificial CSF (aCSF, Ctl) administration over 72h. Left, illustration of the subcutaneous pump/catheter and intraventricular catheter placement. Right, schematic demonstrating pump/catheter placement and resulting ventricular changes. CC, corpus callosum, AC, anterior commissure. (B) Representative immunohistochemical images showing lateral ventricles 72h after infusion of control, E. coli+LPS, E. coli−LPS, or LPS (DAPI, blue). (C) Quantification of lateral ventricular size (% brain volume) after 72h infusion of aCSF, E. coli+LPS, E. coli−LPS, or LPS. Volume was calculated from sequential slices through the entire lateral ventricular system (n=5-7 animals per condition; see Methods). (D) Ventricular system infusion of Evans blue dye (injected into the LV of Ctl and LPS-treated animals), demonstrating flow through cerebral aqueduct (CA) and fourth ventricle (4V). (E) Body weight-normalized CSF secretion rates (μL/min/kg) in control (aCSF), E. coli+LPS (24h, 48h, or 72h), E. coli−LPS, LPS (72 h), or LPS + bumetanide (72 h)-treated animals (n=3-6 animals per condition). (F) Representative immunohistochemical images of LVs in Ctl vs LPS-treated Tlr4+/+ and Tlr4−/− rats (DAPI, blue). (G) Quantitation of LV size (% brain volume) in Ctl and LPS-treated Tlr4+/+ and Tlr4−/− rats (n=5-6 animals per condition). (H) Body weight-normalized CSF secretion rates (μL/min/kg) of Tlr4+/+ Ctl, Tlr4+/+ LPS-treated, Tlr4−/− Ctl, and Tlr4−/− LPS-treated rats (n=4-6 animals per condition). 2.5x mag, scale bars 0.25m. Error bars, mean ± sem; each symbol represents one animal. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, ns = not significant, by one-way ANOVA.